The life of a drug-related patent is normally 20 years from its filing date. However, the drug development process takes around 12-15 years. Thus, the average effective patent life for a new drug—the amount of time where the product is sold under patent protection—is roughly 10 to 12 years. The Drug Price Competition and Patent Term Restoration Act of 1984, also referred to as the “Hatch-Waxman Act,” allows the life of a drug product to be extended to compensate for the delay in obtaining U.S. Food and Drug Administration (FDA) approval, but the extension is limited to five years.
In addition to the direct costs of development, firms must pay returns on the capital that they invest on behalf of shareholders over the course of a decade or more, a cost that increases as development timeframes increase (Masia, Neil. “The Cost of Developing a New Drug.” U.S. DEPARTMENT OF STATE Bureau of International Information Programs, Focus on Intellectual Property Rights, 2006. 82-83).
A report by the Federal Trade Commission has identified the cost of developing a new drug at five million to two billion dollars, with vaccines costing even more (Presentation, Adams, Christopher, Federal Trade Commission. “Spending on New Drug Development”, Jan. 26, 2008, http://www.idei.fr/doc/conf/pha/conf—2008/adams.ppt, retrieved on 1 Apr. 2009). Independently, the Tufts Center for the Study of Drug Development estimates the cost to develop biologic products at $1.2 billion (“Cost to develop new biotech products is estimated to average $1.2 billion”, Tufts Center for the Study of Drug Development Impact Report, Kaitin K I, editor. 2006 November/December; 8(6)). (In the U.S., a biological product is defined as “a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product . . . , applicable to the prevention, treatment or cure of a disease or condition of human beings” (Public Health Services Act 42 U.S.C. §262(i)).)
FIG. 29 shows the significant components of the drug development process. After a promising compound has been identified during the process of drug discovery, the development phase begins with the nonclinical phase (animal studies), with goals of determining a compound's probability of success, understanding its potential adverse effects in humans, and determining dosing amounts and delivery methods that will allow safe testing in humans.
After sufficient data has been gathered, a drug company submits an Investigational New Drug Application (IND) to the FDA, providing data showing that it is reasonable to begin tests of a new drug on humans New information is provided to the FDA every month until the drug is approved. New information submitted to the FDA is called a “submission.” There could be over 500 submissions for an IND application. For cancer drugs, on average it takes 8 years from the start of clinical trials (human testing) to approval to market the product.
The Clinical phase of drug development is intended to prove that the drug is safe and effective for its proposed use. If there are existing drugs on the market that are for the same purpose as the investigational new drug, the investigational new drug must provide evidence that it is superior to the already approved drug. For both safety and economic reasons, clinical development takes place over several phases:
Phase 1: Involves the initial introduction of an investigational new drug into humans. These studies are closely monitored and may be conducted in patients, but are usually conducted in healthy volunteer subjects. These studies are designed to determine the initial effect, risks, and, if possible, to gain early evidence on effectiveness. The total number of subjects included in Phase 1 studies varies with the drug, but is generally in the range of 20 to 80.
Phase 2: Studies are conducted to obtain some preliminary data on the effectiveness of the drug for a particular purpose (indication) with patients who have the disease or condition. This phase of testing also helps determine the common short-term side effects associated with the drug. Phase 2 studies are typically well-controlled, closely monitored, and conducted in a relatively small number of patients, usually involving several hundred people.
Phase 3: Studies are expanded controlled and uncontrolled trials. They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained in Phase 2, and are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug. Phase 3 studies also provide an adequate basis for extrapolating the results to the general population and transmitting that information in the physician labeling. Phase 3 studies usually include several hundred to several thousand people.
There could be anywhere from several hundred to fewer than one thousand studies performed to show that a product is safe and effective with over a million data points. Each study stores the data points differently, thereby making it extremely difficult to perform analysis across studies and across products. Each study can potentially be run by a different organization and can store and collect data differently.
A clinical trial protocol (protocol) is a document that describes the objective(s), design, methodology, statistical considerations, and organization of a clinical trial. The protocol contains a study plan on which the clinical trial is based. The protocol describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study. When analyzing the clinical study data, it can be very difficult and time-consuming to quickly and accurately determine if the protocol was properly followed. The protocol is also referred to herein as the “study definition.”